Statistics on causes of death and rates of hospitalization and treatment in the world show that cerebrovascular diseases always rank high. In particular ischemic cerebrovascular diseases are recently increasing as compared with hemorrhagic cerebrovascular diseases. An ischemic cerebrovascular disease is choking of the cerebral blood flow by some causes, ultimately resulting in necrosis of the cerebral tissue. Inter alia, neuronal cells are vulnerable and therefore ready to die on occurrence of ischemia. Neuronal cell death due to ischemia is known to be the most common condition leading to falling off of nerves due to cerebral disturbance (see Shinkei Shinpo, Vol. 36(2), pp. 225-235 (1992) and Dementia, Vol. 7, pp. 161-171 (1993). Hence, a substance which prevents neuronal cell death is believed to create a therapeutic and prophylactic agent effective on cerebrovascular disease. However, such an agent having sufficient efficacy has not yet been found.
It is known that similar neuronal cell death also accompanies traumatic head injury and postencephalitis (see J. Neurosurq., Vol. 67, pp. 110-119 (1987), Shinken Shinpo, Vol. 35(5), pp. 705-716 (1991), and Taisha, Vol. 26, pp. 253-257 (1989)). Accordingly, prevention of neuronal cell death is considered to be treatment and prevention effective on these diseases
Recently, dementia has been recognized as social problem with the increase of aging society. Dementia is classified types of pathology as dementia of Alzheimer type or dementia of cerebrovascular type. Both of them accompany clinically disturbance of intelligence as basic manifestation (amnesia, disturbance of memorization, disorientation, fugue, etc.) and delirium including phantasm and hallucination, delusion, aggressive behavior, strain, agitation or hypobulia as manifestation caused by disturbance of intelligence. For the purpose of improving the manifestation caused by dementia, agents for improving brain metabolism and agents for improving cerebral circulation have been put to practical use. However, the efficacy is not enough because the above agents are not effective for disturbance of intelligence as basic manifestation of dementia and development of more effective medicaments has been waited.
On the other hand, it is known that the aminobenzensulfonic acid derivatives being represented by the following formula (I):
(wherein R1 represents hydrogen atom, C1-C6 alkyl group, C3-C7 cycloalkyl group, C1-C4 halogenated alkyl group, halogen atom or C6-C12 aryl group, R2 represents hydrogen atom, C1-C6 alkyl group, or C7-C12 aralkyl group which may also have at least one substituent selected from the group consisting of cyano groups, nitro groups, C1-C6 alkoxy groups, halogen atoms, C1-C6 alkyl groups and amino groups, and n represents an integer of 1 to 4) have an effect of inhibiting overaccumulation of intracellular calcium ions (Japanese Patent Application Publication Nos. 7263/1991, 139127/1992, 221479/1997 and 298077/1998, European Patent Application Publication Nos. 390654 and 779283, and U.S. Pat. Nos. 5,053,409 and 5,990,113) and an effect of improving calcium ion uptake of cardiac sarcoplasmic reticulum (International Patent Application Publication No. WO 99/40919).
It has been disclosed that such compounds may be useful for prevention or treatment of ischemic heart diseases such as myocardial infarction and angina, heart failure, hypertension and arrhythmia. However, any of these publications neither suggested nor stated that these compounds may be useful for prevention or treatment of nervous system disorder.